Current Issue : July - September Volume : 2013 Issue Number : 3 Articles : 6 Articles
Structural and functional changes affecting the aging kidney predispose to an increased risk of Acute Kidney Injury (AKI) in the elderly, a condition which is becoming more and more relevant with the increase in life expectancy. The epidemiology of AKI in the elderly is not well assessed, because of the variable etiology, the coexistence of several comorbidities, the various clinical settings and geographical areas where the condition is managed, and the lack of uniform definition criteria. Currently, the use of the term AKI is suggested to mean any abrupt reduction in kidney function, while acute renal failure is just meant to indicate severe dysfunctions requiring renal replacement treatment. Comorbidities, common among elderly patients and several age-related conditions are risk factors for AKI. Moreover, also in elderly patients the presence of baseline proteinuria and reduced glomerular filtration rate are both powerful independent risk factors for AKI. Elderly patients with Chronic Kidney Disease (CKD) who develop AKI are at high risk for mortality, non-recovery from AKI and progression to more advanced stages of CKD and even to endstage renal disease. As a consequence, the challenge for nephrologists is to find strategies to either prevent AKI or prevent the transition from AKI to CKD....
Restless Legs Syndrome is a neuropathic disorder seen in end stage renal disease. Since biotin is dialyzable, we examined the relationship between biotin status and Restless Legs Syndrome in end stage renal disease (Study 1) and determined the effect of biotin supplementation on Restless Legs Syndrome symptoms (Study 2). Comparison of prevalence of biotin deficiency in those with and without Restless Legs Syndrome (Study 1) and randomized assignment, double-blinded, placebo-controlled study of biotin supplementation (Study 2) were in a medical centerââ?¬â?¢s outpatient dialysis unit. In Study 1, patients received chronic dialysis and routine biotin supplementation at Ã?Å?300 Ã?µg daily (10 times the recommended dietary allowance). In the intervention Study 2, biotin was supplemented at 10,000 Ã?µg daily for 8 weeks; the placebo group received Ã?Å?300 Ã?µg of biotin daily. Outcome was measured by Restless Legs Syndrome symptom score and biotin status as indicated by activation coefficient of the biotin-dependent enzyme propionyl-CoA carboxylase in peripheral blood lymphocytes. In Study 1, patients with (n=30) were more likely than those without (n=19) Restless Legs Syndrome to be biotin deficient as judged by increased activation coefficient of propionyl-CoA carboxylase; mean (Ã?± 1SD) was 1.17 Ã?± 0.65 vs. 0.87 Ã?± 0.39, respectively (P=0.007). In Study 2, Restless Legs Syndrome score of the biotin group (n=16), improved from 20 Ã?± 6 to 13 Ã?± 11 (P=0.001). However, in the placebo group (n=15), Restless Legs Syndrome score also improved from 17 Ã?± 8 to 12 Ã?± 10 (P=0.01). Consequently, this change was not different between biotin and placebo. Mean activation coefficient of propionyl-CoA carboxylase of the biotin group (n=8) improved from 1.38 Ã?± 0.76 to 0.81 Ã?± 0.25 (P=0.01) and did not change in the placebo group (0.98 Ã?± 0.44 vs. 1.17 Ã?± 0.32; P=0.17). The improvement of biotin status and of Restless Legs Syndrome score with the 10,000 Ã?µg supplement suggests that large biotin supplements might be necessary to optimize biotin status in dialysis patients....
Background: Prevention of chronic kidney disease (CKD) is a major public health issue. Although several studies\r\nhave been performed on the association between alcohol consumption and CKD or renal function, it remains\r\ncontroversial. Numerous genetic polymorphisms have been reported to be associated with CKD and kidney\r\nfunction. Mitochondrial DNA cytosine/adenine (Mt5178 C/A) polymorphism is associated with longevity in\r\nJapanese. This polymorphism modifies the effects of alcohol consumption on blood pressure, risk of hypertension,\r\nserum triglyceride levels, risk of hyper-LDL cholesterolemia and serum uric acid levels. The objective of this study\r\nwas to investigate whether Mt5178 C/A polymorphism modifies the effects of alcohol consumption on renal\r\nfunction in male Japanese health check-up examinees.\r\nMethods: A total of 394 male subjects aged 29ââ?¬â??76 years were selected from among individuals visiting the\r\nhospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the\r\ncombined effects of Mt5178 C/A polymorphism and habitual drinking on the risk of mildly decreased estimated\r\nglomerular filtration rate (eGFR) (<90 ml/min/1.73 m2) was conducted.\r\nResults: For Mt5178A genotypic men, habitual drinking may increase eGFR (P for trend = 0.003) or reduce the risk of\r\nmildly decreased eGFR (P for trend = 0.003). Daily drinkers had a significantly higher eGFR than non-drinkers (P = 0.005).\r\nThe crude odds ratio for decreased eGFR was significantly lower in daily drinkers than in non-drinkers (odds ratio = 0.092,\r\n95% confidence interval: 0.012-0.727, P = 0.024). On the other hand, for Mt5178C genotypic men, habitual drinking does\r\nnot appear to affect eGFR.\r\nConclusion: The present results suggest a joint effect of Mt5178 C/A polymorphism and alcohol consumption on eGFR\r\nand the risk of mildly decreased eGFR in male Japanese subjects....
Background: Gremlin, a bone morphogenetic protein antagonist, plays an important role in the pathogenesis of\r\ndiabetic nephropathy (DN). However, the specific molecular mechanism underlying Gremlinâ��s involvement in DN\r\nhas not been fully elucidated. In the present study, we investigated the role of Gremlin on cell proliferation and\r\naccumulation of extracellular matrix (ECM) in mouse mesangial cells (MMCs), and explored the relationship between\r\nGremlin and the ERK1/2 pathway.\r\nMethods: To determine expression of Gremlin in MMCs after high glucose (HG) exposure, Gremlin mRNA and\r\nprotein expression were evaluated using real-time polymerase chain reaction and western blot analysis, respectively.\r\nTo determine the role of Gremlin on cell proliferation and accumulation of ECM, western blot analysis was used to\r\nassess expression of pERK1/2, transforming growth factor-�Ÿ1 (TGF-�Ÿ1) and connective tissue growth factor (CTGF).\r\nCell proliferation was examined by bromodeoxyuridine (BrdU) ELISA, and accumulation of collagen IV was\r\nmeasured using a radioimmunoassay. This enabled the relationship between Gremlin and ERK1/2 pathway\r\nactivation to be investigated.\r\nResults: HG exposure induced expression of Gremlin, which peaked 12 h after HG exposure. HG exposure alone or\r\ntransfection of normal-glucose (NG) exposed MMCs with Gremlin plasmid (NG + P) increased cell proliferation.\r\nTransfection with Gremlin plasmid into MMCs previously exposed to HG (HG + P) significantly increased this HGinduced\r\nphenomenon. HG and NG + P conditions up-regulated protein levels of TGF-�Ÿ1, CTGF and collagen IV\r\naccumulation, while HG + P significantly increased levels of these further. Inhibition of Gremlin with Gremlin siRNA\r\nplasmid reversed the HG-induced phenomena. These data indicate that Gremlin can induce cell proliferation and\r\naccumulation of ECM in MMCs. HG also induced the activation of the ERK1/2 pathway, which peaked 24 h after HG\r\nexposure. HG and NG + P conditions induced overexpression of pERK1/2, whilst HG + P significantly induced levels\r\nfurther. Inhibition of Gremlin by Gremlin siRNA plasmid reversed the HG-induced phenomena. This indicates\r\nGremlin can induce activation of the ERK1/2 pathway in MMCs.\r\nConclusion: Culture of MMCs in the presence of HG up-regulates expression of Gremlin. Gremlin induces cell\r\nproliferation and accumulation of ECM in MMCs. and enhances activation of the ERK1/2 pathway....
Background: Polycystin-2 (PC2), encoded by the gene that is mutated in autosomal dominant polycystic kidney\r\ndisease (ADPKD), functions as a calcium (Ca2+) permeable ion channel. Considerable controversy remains regarding\r\nthe subcellular localization and signaling function of PC2 in kidney cells.\r\nMethods: We investigated the subcellular PC2 localization by immunocytochemistry and confocal microscopy in\r\nprimary cultures of human and rat proximal tubule cells after stimulating cytosolic Ca2+ signaling. Plasma membrane\r\n(PM) Ca2+ permeability was evaluated by Fura-2 manganese quenching using time-lapse fluorescence microscopy.\r\nResults: We demonstrated that PC2 exhibits a dynamic subcellular localization pattern. In unstimulated human or rat\r\nproximal tubule cells, PC2 exhibited a cytosolic/reticular distribution. Treatments with agents that in various ways affect\r\nthe Ca2+ signaling machinery, those being ATP, bradykinin, ionomycin, CPA or thapsigargin, resulted in increased PC2\r\nimmunostaining in the PM. Exposing cells to the steroid hormone ouabain, known to trigger Ca2+ oscillations in kidney\r\ncells, caused increased PC2 in the PM and increased PM Ca2+ permeability. Intracellular Ca2+ buffering with BAPTA,\r\ninositol 1,4,5-trisphosphate receptor (InsP3R) inhibition with 2-aminoethoxydiphenyl borate (2-APB) or Ca2+/Calmodulindependent\r\nkinase inhibition with KN-93 completely abolished ouabain-stimulated PC2 translocation to the PM.\r\nConclusions: These novel findings demonstrate intracellular Ca2+-dependent PC2 trafficking in human and rat kidney\r\ncells, which may provide new insight into cyst formations in ADPKD....
Background: Acute kidney injury (AKI) is common in hospitalized human immunodeficiency virus (HIV)-infected\r\npatients and is associated with hospital mortality. We aimed to evaluate the impact of AKI on long-term mortality\r\nof hospitalized HIV-infected patients.\r\nMethods: Retrospective analysis of a cohort of 433 hospitalized HIV-infected patients who were discharged alive\r\nfrom the hospital. AKI was defined according to ââ?¬Ë?Risk Injury Failure Loss of kidney function End-stage kidney diseaseââ?¬â?¢\r\ncreatinine criteria, as an increase of baseline serum creatinine (SCr) X 1.5 or in patients with baseline SCr > 4 mg/dL\r\nif there was an acute rise in SCr of at least 0.5 mg/dL. Cumulative mortality curves were determined by the\r\nKaplan-Meier method, and log-rank test was employed to analyze statistically significant differences between\r\ncurves. Cox regression method was used to determine independent predictors of mortality. Risk factors were\r\nassessed with univariate analysis, and variables that were statistically significant (P < 0.05) in the univariate analysis\r\nwere included in the multivariate analysis.\r\nResults: Sixty-four patients (14.8%) had AKI. Median follow-up was 37 months. At follow-up 81 patients (18.7%)\r\ndied. At 1, 2 and 5 years of follow-up, the cumulative probability of death of patients with AKI was 21.2, 25 and\r\n31.3%, respectively, as compared with 10, 13.3 and 16.5% in patients without AKI (log-rank, P = 0.011). In\r\nmultivariate analysis AKI was associated with increased mortality (adjusted HR 1.7, 95% CI 1.1-3; P = 0.049).\r\nConclusions: AKI was independently associated with long-term mortality of hospitalized HIV-infected patients....
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